We plan to follow our precedent of studying diseases in parallel (i.e. chronic manganese poisoning vs parkinsonism) by investigating extrapyramidal diseases and behavioral disorders. We will execute investigations in animals, their organs or components of their cells to guide the clinical work and vice versa. We specifically propose the following investigations: In animals: a) Tests for each chemical proposed for use in clinical experiments. b) Search for a marker (MN54 or Mn55) for cerebral sensitivity of resistance to selected neuroactive drugs. c) Investigations of genetic determinants in the behavior of the marker. d) Modification of (c) by trace metals, hormones, diet, drugs and elucidation of underlying mechanisms. e) Synthesis of labeled compounds and drug analogs for testing. f) Further development of the combined inorganic plus organic analyses of the same biopsy-size sample of brain. In man: a) Novel anti-parkinson drugs and their toxicity, potency and cerebral side-effects. b) Pharmacological and dietary modification of pharmacological behavioral disorders which might become applicable to idiopathic behavioral disorders if the precedent of pharmacological parkinsonism holds. c) Parallel study of parkinsonism and selected behavioral disorders in an attempt to break the reciprocity between treating the one and inducing the risk of the other.